Cocaine use has reached epidemic proportions in the United States, and sudden death caused by cocaine is a major public health care concern. The causes of sudden death are not clear, and the only interventions available are supportive therapy and treatment of symptoms. Pilot studies suggest that the selective delta-opioid receptor antagonist naltrindole potentiates cocaine-induced lethality in rats. This raises the possibility that the opioid system may be involved in proteCting against sudden death induced by Cocaine in humans. The aim of this study is to define the relationship between the opioid system and cocaine- induced toxicity in the rat. Dependent measures will include lethal dose of cocaine, seizure threshold, mean arterial pressure, and heart rate. The first part of the study will characterize the opioid pharmacology of the interaction through the use of selective opioid-receptor agonists and antagonists. The second part will characterize the stimulant pharmacology of the interaction through the use of representative stimulant and nonstimulant drugs.